Clinical pathology--a workshop report.
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Adult↗
Biomedical subjects
C M Salafia
Publications and source records attributed to C M Salafia.
Antenatal corticosteroids and placental histology in preterm birth.
To assess the effects of antenatal corticosteroid use on placental histopathology, we have reviewed a database of 463 consecutive non-anomalous singleton liveborns delivered at less than 32 weeks between April 1988 and December 1994, of which 280 received one or more doses of corticosteroids for promotion of fetal lung maturation. Patients were grouped by the number of corticosteroid doses received (analyzed as none, 1, 2 and 3 or more doses). Clinical and demographic factors were recorded prospectively. Placental histopathology was reviewed blinded to clinical factors except gestational age, and 42 distinct placental lesions were examined and scored for severity. Data were analyzed by contingency tables, one-way analysis of variance, and linear regression analysis. Among clinical variables, univariate analysis showed that the number of corticosteroid doses was significantly related to presence of labour prior to delivery, pre-eclampsia, premature rupture of membranes and clinical suspicion or diagnosis of chorioamnionitis. Using linear regression analysis with these clinical variables as confounders, increased number of doses of antenatal corticosteroids was related to increased severity of villous fibrosis and stromal mineralization, and fewer villous infarcts.
Adrenal Cortex Hormones↗
Torsade de pointes in a child with acute rheumatic fever.
Ventricular arrhythmias are uncommon in acute rheumatic carditis. We report the case of a child who presented with rheumatic carditis, prolonged corrected QT interval, and torsade de pointes. The episodes of torsade were controlled with beta-blockade and cardiac pacing. The child subsequently died as a result of brain injury; the autopsy revealed classic findings of acute rheumatic carditis.
Adolescent↗
Shortened gestational age following multifetal pregnancy reduction: can chronic placental inflammation be the explanation?
OBJECTIVE: This study tests the hypothesis that chronic inflammatory foci in the placentas of siblings that undergo multifetal pregnancy reduction are associated with shortened gestational length. METHODS: Among 446 patients who underwent multifetal pregnancy reduction (MPR), 56 delivered at Mount Sinai Hospital, 37 (66%) had their placentas referred to surgical pathology and 29 (78%) of the 37 patients had tissue sampled from the placenta of the reduced sibling. Slides were reviewed (by C.M.S.) blinded to clinical data. Lesions were diagnosed using previously published criteria. Specifically, inflammatory lesions were correlated with the various perinatal parameters. Non-parametric testing considered p < 0.05 to be significant. RESULTS: Ten (35%) of 29 patients had chronic inflammation in the reduced placenta. Their gestational age at delivery was 33.1 +/- 3.2 weeks, compared to 35.8 +/- 2.3 weeks in those without chronic inflammation (Z = -2.53, p = 0.01). There was no difference between the cases with and those without chronic inflammation in the reduced placenta, in regard to past reproductive history or clinical assessment of the MPR procedure (e.g. the number of attempts, duration of the procedure, or post-procedural complications). CONCLUSION: The majority of patients who underwent MPR did not develop a chronic inflammatory response to the process of 'resorbing' the placental tissues of the reduced sibling. However, a significant number (35%) of women who delivered viable offspring after MPR had chronic inflammation in the placenta, and had a shortened gestational length.
Chronic Disease↗
Biophysical profile in predicting acute ascending infection in preterm rupture of membranes before 32 weeks.
OBJECTIVE: To assess the performance of the biophysical profile (BPP) and its components within 24 hours of delivery in predicting histopathologic evidence of severe acute placental inflammation in women with premature rupture of membranes (PROM) before 32 weeks' gestation. METHODS: We examined placentas from a series of consecutive, nonanomalous, live-born, singleton infants delivered before 32 weeks' gestation after PROM. In 166 cases, biophysical profiles (BPP) were done within 24 hours of birth. Histologic evidence of acute inflammation was assessed in the maternal (amnion) and fetal (chorionic and umbilical cord vessels) compartments, and scored on a severity scale of 0-4 by a single pathologist masked to clinical data. The presence and severity of acute inflammation was related to BPP results and its individual components. RESULTS: The overall prevalence of severe acute inflammation, ie, a score of 3 or 4, was 59% (98 of 166). In 30 (18%) cases it was present in the amnion, in 49 (30%) cases in chorionic or umbilical cord vessels, and in 19 (11%) cases in maternal and fetal compartments. There was no association between abnormal BPP score and presence or absence of severe acute placental inflammation (48% versus 46%, P =.7). Our study had a 90% power to detect a 0.26 difference between them. When rates of abnormal BPP scores were compared in cases with different degrees of acute inflammation in the maternal, fetal, or both compartments, no association was found. When the individual components of the BPP were analyzed in relation to site and severity of acute inflammation, no association was detected. CONCLUSION: We did not find evidence of a dose-response relationship between acute placental inflammation and BPP score or its individual components in cases of PROM with infants delivered before 32 weeks. Mediators other than infection might affect BPP in preterm PROM.
Acute Disease↗
Chronic intrauterine bleeding and fetal growth at less than 32 weeks of gestation.
Placental hemosiderin deposition representing intrauterine bleeding at least 24-48 h before delivery is detected frequently in prematurity. The objective of this study was to assess incidence and site of histologic evidence of intrauterine bleeding in association with fetal growth in prematurity. Placentas of consecutive nonanomalous singleton liveborns delivered <32 weeks of gestation were studied for the presence of hemosiderin in decidua of the placental basal plate or extraplacental membranes (confirmed by Prussian blue stain). Cases of placenta previa, clinical abruption, or coagulopathy and cases in whom obstetric and neonatal gestational age assessment differed by >2 weeks were excluded. A single reviewer blinded to clinical data except for gestational age at delivery assessed the presence of decidual hemosiderin. Statistical analysis included ANOVA, and Mann-Whitney U test with p<0.05 considered significant. The study included 352 patients delivered for principal indication of premature rupture of membranes (PROM) or preterm labor (PTL) and 78 patients delivered for preeclampsia between 1989 and 1994. Mean birth weight percentiles for neonates delivered following PROM/PTL versus preeclampsia were: no decidual hemosiderin 42+/-25 versus 17.4 +/-25, extraplacental membrane hemosiderin 42+/-25 versus 9.2 +/-10, placental basal plate hemosiderin 42+/-25 versus 17+/-24, and hemosiderin in both sites 27+/-21 versus 6.4+/-10 (p = 0.02). Hemosiderin deposition in both placental basal plate and extraplacental decidua is associated with significantly lower mean birth weight percentiles in PROM/PTL at less than 32 weeks of gestation. We postulate that in these patients placental disruption which accompanies decidual bleeding may explain the relatively impaired fetal growth. In preeclampsia, hemosiderin depositions are not associated with further impaired fetal growth.
Biomarkers↗
A perinatal pathology view of preterm labor.
The development and widespread use of tocolytic agents over the past 2 decades has not appeared to substantially affect the overall incidence of preterm delivery in the United States. Preterm delivery, therefore, remains one of the most poorly controlled and poorly understood mechanisms of perinatal morbidity and mortality and a significant strain on public health resources. The purpose of this review is to examine what is currently understood about the clinical manifestations and indicators of preterm delivery, and what, if any, may be the contribution of placental pathology to the understanding of the structural and functional abnormalities that may precede these clinical signs. Two case studies will be used to show how placental pathology may document a pattern of reproductive failure that eludes current methods of clinical screening. A retrospective analysis of what may have gone wrong in the pregnancies, focusing on the placental lesions, may contribute to a greater understanding of the heterogeneous overall processes behind recurrent idiopathic preterm delivery. Such analysis, in conjunction with known clinical factors, may guide the development of better-directed diagnostics and therapies.
Adult↗
Decidual and vascular pathophysiology in pregnancy compromise.
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Decidua↗
Histologic distribution and biochemical properties of alpha 1-microglobulin in human placenta.
PROBLEM: The embryo is protected from immunologic rejection by the mother, possibly accomplished by immunosuppressive molecules located in the placenta. We investigated the distribution and biochemical properties in placenta of the immunosuppressive plasma protein alpha 1-microglobulin. METHOD OF STUDY: Placental alpha 1-microglobulin was investigated by immunohistochemistry and, after extraction, by electrophoresis, immunoblotting and radioimmunoassay. RESULTS: alpha 1-Microglobulin staining was observed in the intervillous fibrin and in syncytiotrophoblasts, especially at sites with syncytial injury. Strongly stained single cells in the intervillous spaces and variably stained intravillous histiocytes were noted. Solubilization of the placenta-matrix fraction and placenta membrane fraction released predominantly the free form of alpha 1-microglobulin, but, additionally, an apparently truncated form from the placenta-membrane fraction. The soluble fraction of placenta contained two novel alpha 1-microglobulin complexes. CONCLUSIONS: The biochemical analysis indicates the presence in placenta of alpha 1-microglobulin forms not found in blood. The histochemical analysis supports the possibility that alpha 1-microglobulin may function as a local immunoregulator in the placenta.
Electrophoresis, Polyacrylamide Gel↗
Incontinentia pigmenti in a newborn male infant with DNA confirmation.
We report on a woman with incontinentia pigmenti (IP), who had two successive term pregnancies. The first pregnancy ended in the birth of a male infant, who is alive and well at 2 years. A second liveborn male had early postnatal distress and died after 1 day of life, after a fulminating clinical course. Polymorphic microsatellite markers, closely linked to the IP gene on the X chromosome, showed that each son inherited a different X chromosome from his mother. Although in most instances IP appears to be prenatally lethal for the male, the phenotype is not completely known. We propose that the neonatal phenotype may be characterized by lethal disturbances in the hematopoietic and immunologic systems.
Adult↗
Multifetal pregnancy reduction is not associated with an increased risk of intrauterine growth restriction, except for very-high-order multiples.
OBJECTIVE: Our purpose was to investigate whether multifetal pregnancies reduced to twins have an increased risk of intrauterine growth restriction and discordant birth weight. STUDY DESIGN: This retrospective cohort study investigated the rates of birth weight discordance > 20% and intrauterine growth restriction using both twin and singleton birth weight curves in 441 twin deliveries after multifetal pregnancy reduction (233 reduced from triplets, 156 from quadruplets, and 52 from quintuplets or greater) compared with 136 nonreduced dichorionic twins. RESULTS: No significant difference was found in the frequency of birth weight discordance and in the overall incidence of intrauterine growth restriction by both twin and singleton birth weight curves when pregnancies that underwent multifetal pregnancy reduction were compared with the control group. There was, however, an almost twofold increase in the rate of intrauterine growth restriction in pregnancies with a starting fetal number of 5 or more (23.1%) compared with that in those reduced from triplets or quadruplets (12.1%) when the twin curve standard was used (P = .03). This difference disappeared when these groups were compared with a singleton nomogram. CONCLUSION: This study suggests that multifetal pregnancy reduction is not associated with an increased risk of intrauterine growth restriction unless the starting fetal number is > or = 5. This finding provides a further rationale to avoid transferring excessive numbers of preembryos after in vitro fertilization.
Birth Weight↗
In vitro studies of the interactions between platelets and amniotic membranes: a potential treatment for preterm premature rupture of the membranes.
OBJECTIVE: Thus far there is no satisfactory treatment for preterm premature rupture of the amniotic membranes. To evaluate the use of platelets to seal the membranes, we investigated in vitro interactions between platelets and the membranes. STUDY DESIGN: Platelet aggregation in the presence of amnion, chorion, and amniotic fluid was quantified. Platelet adhesion to the fetal membranes was investigated by electron microscopy. In addition, a model system was designed to evaluate the capacity of platelets to seal a standardized puncture in the membranes. RESULTS: Platelets aggregated in response to amnion but not to chorion or amniotic fluid. Adhesion and activation occurred on connective tissues underlying amnion and chorion but not on the amniotic epithelium. Platelets sealed a puncture in fetal membranes, and the platelet plug was visualized by electron microscopy. CONCLUSIONS: Exposed connective tissue of amniotic membranes was demonstrated to trigger platelet adhesion, aggregation, and activation, and platelets were shown to seal a standardized puncture in fetal membranes. Our results indicate that platelets might be useful for treatment of ruptured membranes after needle puncture.
Amnion↗
Clinical correlations of patterns of placental pathology in preterm pre-eclampsia.
The objective of this study was to determine if placental histopathology patterns are associated with clinical features of preterm pre-eclampsia. A 1989-1993 database of consecutive non-anomalous singleton livebirths delivered at 22-32 weeks gestation excluding cases of maternal diabetes mellitus and chronic hypertension included 74 cases of pre-eclampsia. Placentae were scored for uteroplacental vascular lesions and lesions of chronic inflammation and coagulation. Thirteen lesion patterns identified by factor analysis were studied in relation to the clinical features. Severe maternal proteinuria was related to placental chronic inflammation, while lower maternal antepartum platelet counts were related to placental abruption and infarct. Lower birthweight percentile and lighter placentae were related directly to uteroplacental vascular lesions. Diagnosis of HELLP and coagulopathy were less common when chronic inflammation scores were high. Serologic studies related to autoimmunity and maternal blood pressures were unrelated to placental histopathology factors. It is concluded that features of maternal and fetal compromise in preterm pre-eclampsia are related to placental histopathology patterns.
Adult↗
Gestational age-dependent extravillous cytotrophoblast osteopontin immunolocalization differentiates between normal and preeclamptic pregnancies.
PROBLEM: Normal placentation requires modulation of proliferative cytotrophoblast to an invasive phenotype. Preeclampsia is characterized by failed cytotrophoblast invasion and arterial remodeling. Osteopontin (OPN) is an extracellular matrix protein implicated in cell adhesion, spreading, and invasion. METHOD OF STUDY: To investigate gestational age-related OPN expression, placental immunostaining was performed. To investigate the role of OPN in uteroplacental vascular pathology, placental immunostaining from pregnancies with preeclampsia (n = 12), fetal growth retardation (FGR) (n = 8), or both (n = 4) was compared with gestational age-matched controls (n = 24). RESULTS: In non-preeclamptic pregnancies, OPN immunolocalized to basal plate and intervillous cytotrophoblasts from 24-30 weeks (n = 13). In preeclampsia, OPN immunoreactivity was detected from 24-40 weeks. Cytotrophoblasts from FGR placentas were OPN-positive until 30 weeks, unless preeclampsia accompanied the FGR. In this case, cytotrophoblasts were OPN-positive from 24-40 weeks. CONCLUSIONS: The data suggest a role for OPN in cytotrophoblast invasion of the maternal vasculature/extracellular matrix during non-preeclamptic placentation, and OPN may serve as a marker for placental bed remodeling.
Diagnosis, Differential↗
Immunohistochemical localization of carboxypeptidases E and D in the human placenta and umbilical cord.
Carboxypeptidase E (CPE) is highly concentrated in neuroendocrine tissues and is the only carboxypeptidase detected in mature secretory vesicles. Carboxypeptidase D (CPD), a carboxypeptidase with CPE-like activity, is widely distributed in tissues and is present in the trans-Golgi network. Previous work had shown that both CPE and CPD are expressed in the human placenta and that CPD is expressed at much higher levels than CPE. The present work provides evidence for the co-localization of CPE and CPD to basal plate extravillous trophoblasts and maternal uteroplacental vascular endothelial cells, chorionic villous endothelial cells, amnionic epithelial cells, and umbilical venous and arterial smooth muscle cells. Whereas the intensity of CPD immunostaining is similar in the placenta and umbilical cord, CPE staining in the placenta is much weaker than in the umbilical cord, suggesting that CPD plays a more important role in the processing of placental peptides. Immunoelectron microscopy of umbilical venous smooth muscle cells shows subcellular localization of both enzymes to the rough endoplasmic reticulum. In addition, CPE is present just subjacent to the cell membrane. The difference in cellular and subcellular localization between the two enzymes indicates that they perform distinct functions in the processing of placental peptides and proteins.
Carboxypeptidase H↗
Placental vascular lesions and likelihood of diagnosis of preeclampsia.
OBJECTIVE: To test the hypothesis that a range of severity of placental vascular lesions underlies preeclampsia and that the likelihood of its clinical diagnosis increases with the extent and severity of uteroplacental vascular lesions. METHODS: Four hundred sixty-five consecutive placentas of singleton, nonanomalous, live-born infants born before 32 weeks' gestation were examined prospectively, and uteroplacental vascular and related villous lesions were assigned a semiquantitative lesion score based on severity and extent of lesions. The summed scores of individual lesions yielded a total uteroplacental vascular lesion score, ranging from 0 to 21, that was correlated with the odds of a clinical diagnosis of preeclampsia, as well as with potential confounders, including maternal age, race, gestational age at delivery, and birth weight centile. Statistical analysis was performed using contingency tables, one-way analysis of variance, multiple logistic regression, and receiver operating characteristic curve. P < .05 was considered significant. RESULTS: A clinical diagnosis of preeclampsia was present in 78 of 465 (17%) cases. Logistic regression demonstrated that the total uteroplacental vascular lesion score related significantly to the diagnosis of preeclampsia (odds ratio 1.43, 95% confidence interval 1.31, 1.57) and this association was independent of gestational age at delivery and birth weight centile. Preeclampsia was diagnosed in 12 of 284 (4%) cases with no or minimal histologic evidence of placental vascular injury (total score less than 4). Conversely, the diagnosis was not made in 4% of cases despite the presence of extensive placental vascular injury (total score at least 14). CONCLUSION: The likelihood of clinical diagnosis of preeclampsia before 32 weeks increases with progressive impairment of the uteroplacental circulation. Histopathologic examination of the placenta can be used to confirm the diagnosis of preeclampsia.
Adult↗
Placental pathology of absent and reversed end-diastolic flow in growth-restricted fetuses.
OBJECTIVE: To identify placental histopathology associated with absent and reversed end-diastolic flow demonstrated by umbilical artery (UA) Doppler velocimetry in fetal growth restriction (FGR). METHODS: Between January 1989 and June 1995, 64 consecutive, nonanomalous singletons at less than the tenth percentile for birth weight were admitted to the neonatal intensive care unit, with UA Doppler velocimetry obtained within 3 days of delivery; 54 of the 64 (84%) had placental histopathology. Umbilical artery Doppler wave forms were classified as having end-diastolic flow (n = 26), and either absent (n = 20) or reversed end-diastolic flow (n = 8). Blinded review of placental histology scored lesions in categories of intraplacental vaso-occlusion, uteroplacental vascular pathology, chronic inflammation, and coagulation. RESULTS: Using cases of FGR with end-diastolic flow present as the control population, we found that absent end-diastolic flow cases had significantly more fetal stem vessels with medial hyperplasia and luminal obliteration, and cases of reversed end-diastolic flow had significantly more poorly vascularized terminal villi, villous stromal hemorrhage, "hemorrhagic endovasculitis," and abnormally thin-walled fetal stem vessels (each P < .005). CONCLUSION: In FGR, UA Doppler velocity wave forms do not demonstrate a continuum of placental lesions in which reversed end-diastolic flow reflects more severe placental histopathology than absent end-diastolic flow and end-diastolic flow present. As expected, absent end-diastolic flow cases had more occlusive lesions of the intraplacental vasculature. In reversed end-diastolic flow, lesions suggesting vascular remodeling and/or damage by pathologic conditions of intraplacental flow predominated.
Blood Flow Velocity↗
Quantitative differences in arterial morphometry define the placental bed in preeclampsia.
The purpose of this study was to quantitatively analyze normal and preeclamptic uteroplacental vasculature. Myometrial arteries from eight placental bed biopsies from uncomplicated term deliveries and 12 from proteinuric preeclampsia were characterized as uteroplacental, spiral, or basal arteries. Basal lumens within 0.2 mm radius and spiral/uteroplacental lumens within 0.4 mm radius were considered as the same artery. The biopsy area, lumen density, and arterial density (after correction for multiple lumens), lumen area, lumen perimeter, mean wall thickness, inflated diameter, and a slant factor, measuring the obliqueness of arterial transection, and ratios of lumen characteristics to mean wall thickness were analyzed. In preeclamptic cases, there were more basal lumens/mm2 and basal arteries/mm2 (P=.003, P=.03), and more spiral lumens/mm2 and spiral arteries/mm2 (P = .01, P = .03). Basal lumen area (P = .0003) and wall thickness (P = .007), and basal and spiral artery lumen perimeters and inflated diameters (for each, P = .0001, P = .048, respectively) and inflated diameter/wall ratios (P = .04, P = .05) were reduced compared with normal cases. Preeclamptic spiral and basal arteries are more tortuous or densely distributed than normal placental bed arteries, with smaller-caliber lumens and thicker walls. Failure of proper placentation may result in abnormal spatial anatomy in the placental bed. Alternatively, an anatomic variant of spiral and basal arteries may be more susceptible to hemodynamic stresses and endothelial damage and may predispose to preeclampsia.
Arteries↗